|
 
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| REVIEW ARTICLE |
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| Year : 2019 | Volume
: 10
| Issue : 2 | Page : 90-97 |
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Oral squamous cell carcinoma under microscopic vision: A review of histological variants and its prognostic indicators
Sahanaz Praveen Ahmed, Lekshmy Jayan, Thayalan Dineshkumar, Swarnalakshmi Raman
Department of Oral and Maxillofacial Pathology and Microbiology, SRM Dental College, Chennai, Tamil Nadu, India
| Date of Web Publication | 9-Jul-2019 |
Correspondence Address:
Dr. Sahanaz Praveen Ahmed
Department of Oral and Maxillofacial Pathology and Microbiology, SRM Dental College, Bharathi Salai, Ramapuram, Chennai - 600 089, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/srmjrds.srmjrds_57_18
Oral squamous cell carcinoma (OSCC) entails quite noteworthy morbidity and mortality rates instead of immense amount of research and advances. Conventional OSCC can present as several variants that make up in aggregate about 10%–15% of all squamous cell carcinomas. Variants of OSCC frequently arise within the oral cavity. Accurate histopathological identification can assist the clinician to plan a precise treatment, as the prognosis of each of them differs extensively. The overall 5-year survival rate following treatment for OSCC is around 50% in most cases. The foremost prognostic elements are mode of invasion, surgical margins, incidence of lymph node metastasis, extracapsular spread, invasive tumor front grade, and clinical and histologic parameters, which are strongly linked with survival rate. Grading by gross histological differentiation does not influence prognosis, unless deeply invasive margins are evaluated by the pathologist. This review focused on the histopathological variants of OSCC with emphasis on prognostic and predictive indices together with molecular factors linked with survival and prognosis of OSCC patients. Hence, it is advised to use the amalgamation of both clinical and pathological indicators to assess the prognosis. Keywords: Histologic variants, oral, predictive markers, prognosis, prognostic markers, squamous cell carcinoma, survival rate
How to cite this article:
Ahmed SP, Jayan L, Dineshkumar T, Raman S. Oral squamous cell carcinoma under microscopic vision: A review of histological variants and its prognostic indicators. SRM J Res Dent Sci 2019;10:90-7 |
How to cite this URL:
Ahmed SP, Jayan L, Dineshkumar T, Raman S. Oral squamous cell carcinoma under microscopic vision: A review of histological variants and its prognostic indicators. SRM J Res Dent Sci [serial online] 2019 [cited 2023 May 28];10:90-7. Available from: https://www.srmjrds.in/text.asp?2019/10/2/90/262384 |
| Introduction | |  |
Oral squamous cell carcinoma (OSCC) is one of the leading cancers in most Asian countries with global distribution. Natural history, epidemiology, and clinicopathological classification of OSCC have been studied comprehensively, and these annotations have led to improved definitions of precursor and in situ neoplastic variations that have, in turn, contributed to a more complete understanding of the etiological factors and pathobiology of development of this common cancer. There is an increased risk of multiple tumors associated with oral cancer mostly because of (1) recurrence, (2) second field tumor, and (3) second primary tumor. It consists of 90%–95% of all oral malignancies and ranks sixth most common neoplasm in the world.[1] Conventional OSCC can present as several variants that make up in aggregate about 10%–15% of all squamous cell carcinomas (SCCs). The main reason behind the increased morbidity and mortality associated with this disease is the lack of awareness in the normal population about the lesion and that early diagnosis is the key to managing as well as reducing the mortality. Because tissue biopsy followed by histopathological analysis is the gold standard in the diagnosis of any cancer, a better understanding of various histopathological variants of SCC may help us in providing necessary awareness to bring down this disease that is terrorizing us with its deadly effects. Clinical as well as pathological markers act as an adjuvant to this in determining the outcome of the disease. These variants include verrucous carcinoma (VC), adenoid/acantholytic/pseudoglandular SCC, spindle cell/sarcomatoid carcinoma, adenosquamous carcinoma (ASC), basaloid SCC, nasopharyngeal carcinoma, carcinoma cuniculatum, papillary SCC, clear cell carcinoma, and primary intraosseous carcinoma (PIOC). Each of these variants has a unique histomorphological appearance. This is a short exposition aimed to give a brief overview of the different histopathological variants of OSCC and discusses in brief about predictive and prognostic indicators for OSCC. The cytomorphologic features of each of the variants are defined in detail in an attempt to deliver appropriate knowledge to empower distinction of these variants of OSCC to aid in pertinent clinical management.
| Conventional Oral Squamous Cell Carcinoma | | |
“Conventional” SCC comprises variable degrees of differentiation of squamous cells, with well-differentiated cells almost perfectly recapitulating normal squamous epithelium, but indicating basement membrane destruction by nests of tumor cells. SCC shows the following features: disorganized growth, dyskeratosis, loss of polarity, keratin pearls, an increased nuclear-to-cytoplasmic ratio, distinct eosinophilic nucleoli, nuclear chromatin irregularities, and increased mitotic figures (including atypical forms). In poorly differentiated SCC, the number of mitotic figures and necrosis tends to increase. The poorly differentiated lesions only have an ambiguous resemblance to squamous epithelium. A rich inflammatory infiltrate comprising mainly lymphocytes and plasma cells is seen at the epithelium-to-connective tissue junction, together with a dense, desmoplastic fibrous stroma. Perineural invasion (PNI) can be appreciated, with a positive correlation to metastatic potential.
| Verrucous Carcinoma | | |
VC has a misleadingly benign microscopic appearance. Microscopically, the advancing margins of the tumor show wide and elongated rete ridges that seem to push into the underlying connective tissue.[2] These broad and bulbous rete ridges are termed as“elephant foot-” like rete ridges, which show somewhat pushing appearance rather than infiltrative appearance. The epithelium is surprisingly well differentiated without any of the typically associated malignant criteria recognized in SCC. A thick inflammatory infiltrate is seen in the juxtaepithelial region. The cells are organized in an orderly maturation toward the surface, with abundant surface keratosis (orthokeratosis; called “church-spire” keratosis).[3] The keratinocytes seem well differentiated, which stain lightly with eosin, and have a small nucleus. Parakeratotic crypting is a common finding. Mitotic figures are rare finding, and when found, they are not atypical. Dysplasia is usually not found, but if seen, it must be limited to the basal zone.[4]
| Spindle Cell Carcinoma | | |
Spindle cell carcinoma comprises primarily fascicles of anaplastic, spindle-shaped cells. Certain spindle cells possibly give the impression of epithelial elements, but others strongly bear a resemblance to atypical mesenchymal cells. The general picture is comparable to that of an anaplastic fibrosarcoma apart from the inconspicuous squamous element. Squamous component frequently comprises dysplasia of the overlying surface epithelium, but may appear as islands of atypical squamous epithelium amid the spindle cells. As the tumor is polypoid, very minimal invasion is seen into the underlying stroma. Direct transition between the two cell types may be seen.[5] Because of frequent surface ulceration, a neoplastic surface component may be difficult to discern. Metastatic lesions can display only spindle cells or only squamous cells or a blend of both spindle and squamous cells. At times, the area of elongation and spindling seems to arise from the basal epithelial cells, making indistinct any demarcation between the surface epithelial origin and the underlying tumor. Tumor shows both hyper- and hypocellular areas, with plump fusiform cells which can be epithelioid or rounded. Sometimes, giant cells can also be appreciated. Mitotic figures (atypical forms) are effortlessly seen in maximum tumors; however, true tumor necrosis is uncommon.
Chronic inflammatory cells can be seen. Seldom, metaplastic or neoplastic cartilage or bone can be seen.[3]
Serial sections may be necessary to find the areas of unambiguous SCC, and immunohistochemical techniques can be mainly useful in differentiating this tumor from mesenchymal spindle cell malignancies. Spindle cells may not be obviously epithelial appearance; they react for cytokeratin. These are best demonstrated with a pan–keratin antibody such as MNF 116. The tumor cells are negative for smooth muscle actin, actin, desmin, S100 protein, and vimentin.
| Adenosquamous Carcinoma | | |
Histopathologically, this tumor comprises discrete areas or a combination of both SCC and adenocarcinoma or conversion of the SCC to adenocarcinoma. The squamous epithelium shows the following features: intercellular bridging, keratin pearl formation, parakeratotic differentiation, individual cell keratinization, and cellular arrangements showing pavement or mosaic pattern.[6] The glandular component tends to be most noticeable in deeper portions of the tumor. The tumor cells mainly comprise basaloid cells, squamous cells, and undifferentiated cells.[6] The tumor exhibits frequent mitoses, necrosis, and PNI with infiltration to the surrounding tissues. However, inflammatory cell infiltrate at the tumor–stromal border is sparse.
In comparison to basal SCC (BSCC), ASC demonstrates a distinct squamous cell component, absence of basaloid cells with peripheral nuclear palisading, and the presence of glandular differentiation, including intracellular and intraluminal epithelial mucin (mucicarmine-positive material).[3]
| Acantholytic (Adenoid) Squamous Cell Carcinoma | | |
Histopathologically, the lesion shows small islands and sheets of dysplastic epithelial cells in the connective tissue stroma. The epithelial cells illustrate obvious dysplastic features such as cellular and nuclear pleomorphism, hyperchromatism, and altered nuclear–cytoplasmic ratio along with numerous abnormal mitotic figures. The lateral or deep extensions of the epithelium show the specific solid and tubular ductal structures which symbolize the lesion. Pseudoglandular structures contain acantholytic or dyskeratotic epithelial cells (pseudoglandular alveolar areas that are lined by a basal layer of polygonal cells with the central lumina containing detached dyskeratotic acantholytic neoplastic cells, “glassy” keratinocytes).[6] These acantholytic cells may appear extremely bizarre, large, or multinucleated. Sometimes shows keratinization and mucous metaplasia. The intervening connective tissue is very minimal, exhibiting moderate vascularity and minimal chronic inflammatory cell infiltrate.[7]
| Basaloid Squamous Carcinoma | | |
Histologically, this tumor shows infiltration and comprises diverse growth patterns, which include lobular, solid, cribriform, trabecular, cords, nests, and cysts or glands. Neurotropism is seen rarely, but lymphatic and vascular perforations and surface ulcerations are commonly noted. The important diagnostic feature is the basaloid component, incorporating closely opposed pleomorphic cells showing scanty cytoplasm and hyperchromatic nuclei into a lobular pattern with peripheral palisading cells. Comedo necrosis is frequently noted in the core of the neoplastic islands. The basaloid regions are continuous with the regions of squamous differentiation, together with abrupt keratinization in the form of squamous pearls, individual cell keratinization, dysplasia, or SCC. Rarely, areas of spindled SCC may also be seen. The tumor cells are divided by a prominent thick pink hyaline material with small cystic spaces having mucoid-type material. The hyaline material may be arranged in a cylinder, rimmed by cells. In metastatic disease, both basaloid and squamous cell components can be appreciated, but predominantly, basaloid features are seen.[3],[8]
| Nasopharyngeal Carcinoma | | |
Nasopharyngeal carcinoma mainly includes the following histopathological types:
- Keratinizing SCC
- Differentiated nonkeratinizing carcinoma or nonkeratinizing SCC
- Undifferentiated nonkeratinizing carcinoma (poorly differentiated carcinoma, anaplastic carcinoma, and lymphoepithelioma).[2]
The microscopic features of keratinizing SCC are same as that of SCC. Keratinization must be markedly evident at the light microscopic level.
In the differentiated nonkeratinizing carcinoma, the tumor cells are squamous in nature and comparatively mature, but there is no keratin production. The cells are oval or round and arranged in papillary and plexiform pattern.
In the undifferentiated nonkeratinizing carcinoma, the tumor comprises sheets of undifferentiated cells with blurry margins, scant cytoplasm, and large, vesiculated nuclei. These tumor cells are seen intermixed with the lymphoid cells generally found at this anatomic site.[9]
When more than one histopathologic type is present, the tumor is classified according to the predominant type.
| Carcinoma Cuniculatum | | |
Microscopically, both exophytic and endophytic growth patterns are seen in this tumor, in which the well-differentiated squamous cells infiltrate deep into the underlying connective tissue. The cells are arranged in tunnels or crypts, which resembles a rabbit burrow (cuniculus), and they are filled with keratotic debris. A particular and diagnostic characteristic is the occurrence of complex branching keratin-filled crypts. Layers of both ortho- and parakeratotic horns are seen, which resembles onion rings, and have numerous foci of microabscesses. However, the basement membrane is intact with a single basal layer; the apparition of little zones of invasion defines the transformation into epidermoid carcinoma. Few areas exhibit lymphoplasmacytic inflammatory infiltrate. Koilocytic changes are absent.[10],[11]
| Papillary Squamous Carcinoma | | |
Histologically, this tumor demonstrates papillary pattern which entails numerous, thin, delicate filiform or finger-like papillary projections. The papillae enclose a delicate fibrovascular core bordered by the neoplastic epithelium. Features such as architectural disruption and distortion, dyskeratosis, surface keratinization, nuclear enlargement, prominent nucleoli, numerous mitotic figures, increased nuclear-to-cytoplasmic ratio, and stromal invasion are frequently noted. The invasion is lacking vascular, perineural, or osseous invasion. An associated rich chronic inflammatory response is frequently present. Koilocytic atypia is commonly noted, characterized by hyperchromatic, crenated nuclei encircled by a clear halo of the cytoplasm and an accentuated cell border.[3] Two types of papillary squamous carcinoma have been defined in the past, a broad-based exophytic form and a papillary form.[12]
| Clear Cell Carcinoma | | |
Clear cell carcinoma is classified into three histologic types: keratinizing (Type I), nonkeratinizing (Type II), and pleomorphic (Type III). There is no evidence of either glycogen or mucin in tumor cells in any of the three histologic types.[13]
Type I or the keratinizing type is characterized by the islands or sheets of tumor cells in a fibrous stroma, with a scant lymphocytic infiltrate. Tumor cells are clear, with nuclei pushed to the periphery, and sometimes indistinguishable from adipocyte. Some tumor cells resemble sebaceous cells showing bubbled cytoplasm. Distinguishing features include foci of keratinization and keratin pearls.
Type II or nonkeratinizing type is characterized by tumor cells arranged in anastomosing cords in a dense fibrous stroma with inflammatory infiltrate mainly comprising plasma cells and lymphocytes. The tumor cells possess a centrally placed nuclei and reticulated clear cytoplasm, and sometimes, central necrosis may also be evident in the tumor cords. These variant does not show any mark of keratination.
Type III or pleomorphic type exhibits striking pleomorphism with extensive vascular and PNI. Foci of squamous differentiation and microcysts with acantholytic tumor cells may be seen.[14]
| Primary Intraosseous Carcinoma | | |
PIOC was initially believed to be a variant of SCC without the characteristic keratinization. However, there are reports of cases of solid PIOC showing keratinization without cystic or odontogenic component. The histopathological features of PIOC are inimitable, with either an alveolar or a plexiform pattern lined peripherally by tall columnar cells with characteristic palisading pattern as in ameloblastoma, which is suggestive of an odontogenic lineage. PIOCs originating from the odontogenic cysts show stratified squamous epithelium showing neoplasia as well as cystic lining. The microscopic picture is, thus, not very pathognomonic, and the microscopy consists of all the lesions that produce squamous odontogenic epithelium, for example, acanthomatous ameloblastoma, squamous odontogenic tumor, and benign and malignant salivary gland tumors that present with squamous metaplasia.[15]
| Prognostic and Predictive Indicators for Oral Squamous Cell Carcinoma | | |
The term prognosis was derivative of the Greek word “gignosko” meaning “to know.” It is defined as “the prediction of probable cause, duration, and outcome of disease based on the general knowledge of the pathogenesis of the disease and the presence of risk factors for the disease.”[16] Various authors have tried to illustrate the relationship of some independent factors or cluster of factors with the prognosis of patients with OSCC. However, not a single factor can alone influence the prognosis of an individual with OSCC. While defining the prognosis of an individual with OSCC, all the Prognostic and predictive indicators for oral squamous cell carcinoma have been tabulated in [Table 1]. | Table 1: Prognostic and predictive indicators for oral squamous cell carcinoma
Click here to view |
| Demographic Factors | | |
Several demographic factors are known to affect prognosis and survival. Young people (below 45 years) are known to have better survival. While the role of gender is not clear, single and divorced persons have poor survival rates.[17] African Americans were almost twice as likely to present with the terminal stage carcinoma.[18] Socioeconomic status also plays an important role. The outcome is fairly shoddier for patients with poorer socioeconomic status and education, most likely because of worse oral hygiene and more difficulty in getting proper medical care. Tobacco consumption had a significant influence on the prognosis of oral cancer patients, and continuing to smoke after treatment contributes to poor survival.[19]
According to various studies conducted, patients with drinking habit accompanied with alcohol-related systemic health issues have bad prognosis compared with nonalcoholics or patients without a history of systemic health problems.[20] Termination of smoking and drinking alcohol led to a noteworthy reduction in mortality at 3 and 5 years.
| Factors Related to the Patient's General Medical Condition | | |
Comorbidity
Comorbidity is defined “as the presence of one or more additional diseases or disorders co-occurring with a primary disease or disorder, in the countable sense of the term. Multiple mechanisms have been utilized to characterize comorbidity.” According to the study conducted by Piccirillo et al., 24% of patients with head-and-neck cancer had moderate or severe comorbidity. Conditions with moderate comorbidity are poorly controlled hypertension, only stroke, and history of an alcoholic seizure. Conditions with severe comorbidity include congestive heart failure or myocardial infarction within the past 6 months, recent stroke, and severely decompensated alcoholism.[16],[21]
Nutrition and oral cancer
Several epidemiological studies have shown the significance of nutrition and diet in oral neoplasia. Foods containing nitrosamines have increased risk of neoplasia, for example, processed meat and red meat. Vegetables and fruits (rich in beta-carotene and high in Vitamins A and C with antioxidant property) are described as protective in oral neoplasia. High meat intake is accounted for 49% of oral and pharyngeal cancers, low vegetable intake for 65%, and low fruit intake for 54%. Persistent ingestion of foods rich in nitrites and nitrosamines, for example, preserved meats and fish, increases the risk of developing oral cancer. Consumption of fried or broiled foods and employment of microwave cooking increases the risks of oral cancer owing to the formation of heterocyclic amines.[16]
Anemia and oral cancer
Patients undergoing radiation therapy for cancer and associated anemia are seen to have worsened prognosis due to low tissue oxygenation. Studies have shown that hemoglobin is one of the important indicators for survival and local control. Normal hemoglobin level for men and women is 14.5 g/dl and 13 g/dl, respectively, and is seen to be associated with improved locoregional and survival control.[16] Iron-deficiency anemia and Plummer–Vinson (Paterson–Brown–Kelly) syndrome result in atrophy of oral epithelium and have shown an association with upper aerodigestive tract carcinoma.
| Pathological Prognostic Implicators of Oral Squamous Cell Carcinoma: Factors Related to Primary Tumor | | |
Tumor dimension
Tumor/node/metastasis staging of head-and-neck cancer is determined by the extension and size of tumor. Clinically, the dimension of tumor represents the greatest surface diameter in a mucosal tumor, whereas pathologically, in resected specimens, it shows the greatest cross-sectional diameter. Studies done by Jadhav et al. showed that patients with tumor dimension <2 cm had a better prognosis and a disease-free survival of 3 years when compared to patients with tumor diameter >2 cm.[16]
Infiltration depth and tumor thickness
“Tumor infiltration depth” explains the degree of cancer progression or growth into the tissue underneath an epithelial surface. The juxtaposition of tumor cells to blood vessels and lymphatics is the main indicator and determining factor of increased risk of nodal metastases and facilitates the tumor's ability to expand.[22]
Tumor thickness concerns the entire tumor mass. Tumor thickness (TT) is another reliable predictor of nodal metastasis.[23] Various studies have proved that tumor depth surpassing 5 mm had a higher metastatic rate (approximately 64.7%), when compared with tumor depth of <5 mm (approximately 5.9%). This accounts for the fact that, in deeper connective tissue, the existence of lymphatic channels paves the way for cervical metastasis.[24] In general, median TT varies between 1.5 and 8 mm for T1 and T2 cancers. When TT exceeds more than 4 mm, the prognosis worsens.[25]
Usually, the TT is calculated with a microscope. It is recorded from the granular layer of the covering epithelium up to the deepest invasive tumor cell layer. The tumor was categorized as superficial lesions, intermediate lesions, and deep lesions according to the thickness. Superficial lesions measured 0–0.76 mm, intermediate lesions were 0.76–1.50 mm, and deep lesions were those which had tumor thickness more than 1.50 mm. Superficial lesions showed 98% of 5-year disease-free survival.[26]
Total tumor volume
Total tumor volume (TTV) also acts as a prognostic indicator and is measured by computed tomography scan. TTV of <6 cm had improved local control over tumor progression.[27]
Excision margins
Excision margin is referred to as the closest proximity of cancer cells to the edge of the normal tissues neighboring the tumor. One of the risk factors for local recurrence in OSCC is the existence of some residual cancer cells at the surgical margins. When the pathologist finds cancer cells at the edge of the tissue, this is described as positive margins and this indicates as aggressive tumor. From a surgical point of view, a margin >5 mm is clear, 1–5 mm is close, and <1 mm is involved. The presence of dysplasia at the margin is related to a suggestively high risk of local recurrence.[28]
The occurrence of positive margins anticipated poor overall survival for oral carcinomas. Intraoperative use of frozen sections for determining margin status reduced the local recurrence. Patients with clear margins had a survival rate of 69% at 5 years compared to 58% with close and 38% with involved margins.
| Factors Related to Histopathology | | |
Pathological grade (degree of differentiation)
There is constant evidence of the value of tumor grade in defining prognosis. Higher grades equate to a poor prognosis. Grading is based on the extent of resemblance of the invading carcinoma to the normal epithelium and its ability to form keratinizing islands. The tumor is graded as well, moderately, or poorly differentiated carcinomas. Most oral carcinomas are moderately differentiated. However, this pathological grading system is widely used and is listed in the current AJCC Staging Form. The system suffers from interexaminer variability and sampling errors. Prognostically, useful Bryne's malignancy grading system has been used to prognosticate oral cancers.[29],[30]
Perineural invasion
PNI of the small nerves is an important predictor of the outcome of patients and is a sensitive indicator for regional recurrence and distant metastasis. Various definitions have been proposed for PNI. Batsakis (1985) defined PNI as tumor cell invasion in, around, and through the nerves. Liebig et al. in addition to the definition of Batsakis added “tumor in close proximity to nerve and involving at least 33% of its circumference or tumor cells within any of the three layers of the nerve sheath.” PNI was considered as positive on finding tumor cells in the perineural space or epineurium.[31]
The presence of PNI has also been shown to mark late-stage disease and also helps make a conclusion about adjuvant radiotherapy, so that a subgroup of node-negative patients are benefited.[32] Recent studies on neurotrophic factors such as nerve growth factor (NGF); adhesion molecules such as neural cell adhesion molecule, intercellular adhesion molecules-5 (telencephalon), and tight junction molecule claudin-1; and extracellular matrix proteins such as laminin-5 have been associated with increased PNI in OSCC. Overexpression of NGF or TrK is significantly associated with clinicopathologic parameters such as positive PNI, larger tumor size, higher clinical stage, and decreased survival rates.[33]
Vascular invasion
It is defined as “the presence of neoplastic cells within an endothelial cell-lined channel.” This is seen in more than 50% of head-and-neck SCCs. It associates with the incidence of concomitant cervical metastases and revealed an increased risk of distant metastatic disease. The scalp and face are commonly affected by metastases, signifying that blood vessels affect the spread of metastases.[34]
| Factors Associated With Cervical Lymph Nodes | | |
Number of positive lymph nodes
Microscopically, the presence of positive lymph nodes signifies the most potent marker for head-and-neck cancer. It also signifies the risk of distant metastasis and local recurrence. The presence of lymph node metastasis in OSCC patients shows a decreased survival rate. The incidence of contralateral metastasis confirms the aggressive nature of the tumor. Mamelle et al. in their study stated that extracapsular extension was an independent interpreter of poor survival.[35] Various authors suggested that extracapsular spread should be merged into pathological staging systems. The capsular rupture has the most noteworthy prognostic influence.[36]
Nodal location and nodal size
Mamelle et al. defined sentinel lymph node as “those nodal groups that provide the primary lymphatic drainage for a particular site within head and neck.” Survival rate was seen to be decreased in patients who showed nodal metastasis external to the sentinel lymph node. Involvement of the lower neck lymph node showed higher chances of the distant metastasis. Mamelle et al. stated that as the node size increased (more than 2 cm in diameter), the risk of local recurrence was also seen to be increased.[35]
| Molecular Prognostic Factors | | |
Proto-oncogene is a normal gene which changes to an oncogene due to mutation. This mutated proto-oncogene and its protein products transform normal cell to a cancer cell where the regulatory process controlling cell division is unresponsive. The tumor suppressor genes inhibit proliferation. Molecular biomarkers show biological alterations between cancers and help predict patient outcome. In the past three decades, more than one hundred molecular biomarkers were identified (by immunohistochemistry) as predictors for OSCC. Different biomarkers include p53, p16, VEGFs, cyclin D1, Ki67, DNA aneuploidy, survivin, MMP9, MKI67, CDKN2A, HPV16, TP53, EGFR, Myc, FAS, and VIM.[37]
Loss of heterozygosity
Loss of heterozygosity (LOH) is a genetic event, usually seen in the cancer cells. It is defined as the “loss of one allele of a genetic locus caused by deletion mutation or loss of a chromosome from a chromosome pair.” Various studies have shown that LOH is a definite marker for the prognosis of head-and-neck cancer. LOH at the 3p region in early stage of OSCC was significantly correlated with reduced disease-free and overall survival.
| Conclusion | | |
OSCC has a greater susceptibility for metastasis to the regional lymph nodes through vascular invasion, thus leading to locoregional failure. Several histopathological predictors such as vascular invasion, PNI, and lymph node involvement aid in forecasting the outcome and the behavior of OSCC. Suitable recognition of the histological variants is a vital factor in the treatment of SCC as VC needs less aggressive treatment when compared to conventional SCC. The recognized prognostic aspects denote a relatively complete understanding of factors linked to survival rate in OSCC patients and offer an additional instrument for selecting patients who need more aggressive treatment strategy.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Pérez-Sayáns M, Somoza-Martín JM, Barros-Angueira F, Reboiras-López MD, Gándara Rey JM, García-García A, et al. Genetic and molecular alterations associated with oral squamous cell cancer (Review). Oncol Rep 2009;22:1277-82.  |
| 2. | Neville BW, Damm DD, Chi AC, Allen CM. Oral and Maxillofacial Pathology. St. Louis; Elsevier Health Sciences; 2015. |
| 3. | Thompson LD. Squamous cell carcinoma variants of the head and neck. Curr Diagn Pathol 2003;9:384-96. |
| 4. | Asha ML, Vini K, Chatterjee I, Patil P. Verrucous carcinoma of buccal mucosa : A case report. Int J Adv Health Sci 2014;1:19-23. |
| 5. | Biradar MV, Dantkale SS, Abhange RS, Kamra HT, Birla K. Spindle cell carcinoma of the tongue: A rare variant of squamous cell carcinoma. Ecancermedicalscience 2014;8:447. |
| 6. | Singh J. Histopathology of oral squamous cell carcinoma – A review. TMU J Dent 2014;1:141-4. |
| 7. | Nayak SD, Jose M, Sequeira J. Oral adenoid/acantholytic squamous cell carcinoma: A report of two cases with review of literature. Kathmandu Univ Med J (KUMJ) 2012;10:83-7. |
| 8. | Pereira MC, Oliveira DT, Landman G, Kowalski LP. Histologic subtypes of oral squamous cell carcinoma: Prognostic relevance. J Can Dent Assoc 2007;73:339-44. |
| 9. | Jeyakumar A, Brickman TM, Jeyakumar A, Doerr T. Review of nasopharyngeal carcinoma. Ear Nose Throat J 2006;85:168-70, 172-3, 184. |
| 10. | Shakil M, Mohentesham I, Jose M, Prabhu V. Carcinoma cuniculatum of the oral cavity- A rare entity. J Adv Med Dent Scie 2014;2:124-6. |
| 11. | Datar UV, Kale A, Mane D. Oral carcinoma cuniculatum: A new entity in the clinicopathological spectrum of oral squamous cell carcinoma. J Clin Diagn Res 2017;11:ZD37-9. |
| 12. | Fitzpatrick SG, Neuman AN, Cohen DM, Bhattacharyya I. Papillary variant of squamous cell carcinoma arising on the gingiva: 61 cases reported from within a larger series of gingival squamous cell carcinoma. Head Neck Pathol 2013;7:320-6. |
| 13. | Nainani P, Singh HP, Paliwal A, Nagpal N. A rare case report of clear cell variant of oral squamous cell carcinoma. J Clin Diagn Res 2014;8:QD07-9. |
| 14. | Kuo T. Clear cell carcinoma of the skin. A variant of the squamous cell carcinoma that simulates sebaceous carcinoma. Am J Surg Pathol 1980;4:573-83. |
| 15. | Sengupta S, Vij H, Vij R. Primary intraosseous carcinoma of the mandible: A report of two cases. J Oral Maxillofac Pathol 2010;14:69-72. [ PUBMED] [Full text] |
| 16. | Jadhav KB, Gupta N. Clinicopathological prognostic implicators of oral squamous cell carcinoma: Need to understand and revise. N Am J Med Sci 2013;5:671-9. |
| 17. | Warnakulasuriya S, Mak V, Möller H. Oral cancer survival in young people in South East England. Oral Oncol 2007;43:982-6. |
| 18. | Swerdlow AJ, Marmot MG, Grulich AE, Head J. Cancer mortality in Indian and British ethnic immigrants from the Indian subcontinent to England and Wales. Br J Cancer 1995;72:1312-9. |
| 19. | Jerjes W, Upile T, Radhi H, Petrie A, Abiola J, Adams A, et al. The effect of tobacco and alcohol and their reduction/cessation on mortality in oral cancer patients: Short communication. Head Neck Oncol 2012;4:6. |
| 20. | Deleyiannis FW, Thomas DB, Vaughan TL, Davis S. Alcoholism: Independent predictor of survival in patients with head and neck cancer. J Natl Cancer Inst 1996;88:542-9. |
| 21. | Piccirillo JF, Lacy PD, Basu A, Spitznagel EL. Development of a new head and neck cancer-specific comorbidity index. Arch Otolaryngol Head Neck Surg 2002;128:1172-9. |
| 22. | Hegde P, Roy S, Shetty T, Prasad BR, Shetty U. Tumor infiltration depth as a prognostic parameter for nodal metastasis in oral squamous cell carcinoma. Int J Appl Basic Med Res 2017;7:252-7. |
| 23. | Moore C, Kuhns JG, Greenberg RA. Thickness as prognostic aid in upper aerodigestive tract cancer. Arch Surg 1986;121:1410-4. |
| 24. | Woolgar JA. T2 carcinoma of the tongue: The histopathologist's perspective. Br J Oral Maxillofac Surg 1999;37:187-93. |
| 25. | Warnakulasuriya S. Prognostic and predictive markers for oral squamous cell carcinoma: The importance of clinical, pathological and molecular markers pathological grade (Degree of differentiation). Saudi J Med Med Sci 2014;2:12-6. [Full text] |
| 26. | Fukano H, Matsuura H, Hasegawa Y, Nakamura S. Depth of invasion as a predictive factor for cervical lymph node metastasis in tongue carcinoma. Head Neck 1997;19:205-10. |
| 27. | Massano J, Regateiro FS, Januário G, Ferreira A. Oral squamous cell carcinoma: Review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:67-76. |
| 28. | van Es RJ, van Nieuw Amerongen N, Slootweg PJ, Egyedi P. Resection margin as a predictor of recurrence at the primary site for T1 and T2 oral cancers. Evaluation of histopathologic variables. Arch Otolaryngol Head Neck Surg 1996;122:521-5. |
| 29. | Odell EW, Jani P, Sherriff M, Ahluwalia SM, Hibbert J, Levison DA, et al. The prognostic value of individual histologic grading parameters in small lingual squamous cell carcinomas. The importance of the pattern of invasion. Cancer 1994;74:789-94. |
| 30. | Sawair FA, Irwin CR, Gordon DJ, Leonard AG, Stephenson M, Napier SS. Invasive front grading: Reliability and usefulness in the management of oral squamous cell carcinoma. J Oral Pathol Med 2003;32:1-9. |
| 31. | Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: A review of the literature. Cancer 2009;115:3379-91. |
| 32. | Miller ME, Palla B, Chen Q, Elashoff DA, Abemayor E, St. John MA, et al. Anovel classification system for perineural invasion in noncutaneous head and neck squamous cell carcinoma: Histologic subcategories and patient outcomes. Am J Otolaryngol 2012;33:212-5. |
| 33. | Varsha BK, Radhika MB, Makarla S, Kuriakose MA, Kiran GS, Padmalatha GV. Perineural invasion in oral squamous cell carcinoma: Case series and review of literature. J Oral Maxillofac Pathol 2015;19:335-41. [ PUBMED] [Full text] |
| 34. | Wong CY, Helm MA, Kalb RE, Helm TN, Zeitouni NC. The presentation, pathology, and current management strategies of cutaneous metastasis. N Am J Med Sci 2013;5:499-504. |
| 35. | Mamelle G, Pampurik J, Luboinski B, Lancar R, Lusinchi A, Bosq J. Lymph node prognostic factors in head and neck squamous cell carcinomas. Am J Surg 1994;168:494-8. |
| 36. | Woolgar JA, Rogers SN, Lowe D, Brown JS, Vaughan ED. Cervical lymph node metastasis in oral cancer: The importance of even microscopic extracapsular spread. Oral Oncol 2003;39:130-7. |
| 37. | Almangush A, Heikkinen I, Mäkitie AA, Coletta RD, Läärä E, Leivo I, et al. Prognostic biomarkers for oral tongue squamous cell carcinoma: A systematic review and meta-analysis. Br J Cancer 2017;117:856-66. |
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